It is known that histone acetylation is controlled by the balance of histone acetyltransferase (HAT) and histone deacetylase (HDAC). Recently some HATs and HDACs were identified and reported to play an important role in the regulation of gene expression (Ogryzko, V. V. et al., Cell 87, 953–959, 1996, Brown, C. E. et al., Trends Biochem. Sci. 25(1), 15–19, 2000, Grozinger, C. M. et al., Proc. Natl. Acad. Sci. USA, 96, 4868–4873, 1999).
On the other hand, it has been known that butyric acid having various functions such as cell cycle arrest, morphological normalization of transformed cells and induction of differentiation induces accumulation of a highly acetylated histones in cells and has an HDAC inhibitory activity (Counsens, L. S. et al., J. Biol. Chem. 254, 1716–1723, 1979). In addition, it was found out that Trichostatin A (TSA) which is a microorganism metabolite shows cell cycle arrest and induction of differentiation (Yoshida, M., et al., Cancer Res. 47, 3688–3691, 1987, Yoshida, M. et al., Exp. Cell Res. 177, 122–131, 1988) and induces apoptosis. TSA induces accumulation of a highly acetylated histones in cells, and from the study using partially purified HDAC, it was demonstrated that TSA is a strong HDAC inhibitor (Yoshida, M., et al., J. Biol. Chem. 265, 17174–17179, 1990).
The HDAC inhibitor has functions such as cell cycle arrest, morphological normalization of transformed cells, induction of differentiation, induction of apoptosis and inhibition of angiogenesis, therefore, the effect as an antitumor agent has been expected (Marks, P. A. et al., J. Natl. Cancer Inst., 92, 1210–1216 2000, Kim, M. S. et al., Nature Med., 7, 437–443, 2001). Other than this, various applications have been attempted, for example, for an agent for treatment and improvement of cell proliferative diseases such as infectious diseases, autoimmune diseases and dermatologic diseases (Darkin-Rattray, S. J. et al., Proc. Natl. Acad. Sci. USA, 93, 13143–13147, 1996), an agent for prevention and treatment of progressive neurodegenerative diseases such as Huntington's disease (Steffan, J. S. et al., Nature, 413, 739–743, 2001), enhancement of the expression of an introduced gene (Chen, W. Y. et al., Proc. Natl. Acad. Sci. USA, 94, 5798–5803, 1997) and the like, and it is expected to become an effective medicament.
In recent years, depsipeptide compounds derived from the culture broth of microorganisms having an HDAC inhibitory activity, for example, FK228 (see Non-Patent Reference 1) and the compounds A, B and C represented by the following formulae (see Patent References 1 and 2) have been reported. These compounds have a good HDAC inhibitory activity and are expected as a new type of antitumor agent.

However, even at present, development and production of a medicament whose intensity of activity, stability, pharmacokinetics, toxicity and the like and further improved has been awaited anxiously.    [Non-Patent Document 1] Nakajima, H. et al., “Experimental Cell Research”, Vol. 241, 126–133, 1998    [Patent Document 1] International Patent WO 00/42062    [Patent Document 2] JP-A-2001–348340